Rabbit antibodies prepared against factor VIII (AHF) preparations give precipitin reactions with an antigen present in normal or hemophilic blood but reduced or absent in plasma of patients with von Willebrand's disease. Since the antisera neutralize factor VIII coagulant activity, it was suggested that factor VIII was the specific antigen against which the precipitating antibody in the antisera was directed and it was referred to as the "factor VIII-like" antigen. By complexing a rabbit "factor VIIl" antibody or a naturally occurring human factor VIII antibody to Sepharose 4B we have obtained factor VIII coagulant activity free of "antigen" and "antigen" free of factor VIII coagulant activity. We have also successfully employed a double antibody technique to achieve the separation. While our rabbit antibodies have relatively little factor VIII coagulant neutralizing activity they strongly inhibit the activity in normal plasma that corrects the defective Ristocetin aggregation property of plasma from a patient with severe von Willebrand's disease. We now propose to perform affinity chromatography on a larger scale and also to explore the feasibility of separating the two activities using conventional biochemical methods which so far have only been partially successful in our hands. We are currently developing radio-immune assays for the two activities. This will be followed by attempts to characterize the various intermediate and end stage degradation and catabolic fragments and to set up immunochemical assays for each.